Macrocytic Anemia Due to Excess Alcohol Consumption with Remarkable Improvement by Vitamin B12 Administration

Bando H, Kato Y, Yamashita H, Ogura K and Yada S

Published on: 2025-07-16

Abstract

The case was 56-year-old male with fatigue and pretibial edema. He continued excessive alcohol consumption for long and showed macrocytic anemia as Hb 8.6g/dL and mean corpuscular volume (MCV) 130fL (80-102). Blood concentration revealed lower Vitamin B₁₂ for 137pg/mL (180-914), normal range of folate 4.6ng/mL (4<) and Vitamin B₁ 37.0ng/mL (21.3-81.9). Pulse wave velocity (PWV) was negative for ABI 1.34/1.32 and baPWV 1413/1436 cm/sec. By ultrasound examination for lower extremities, blood flow was unremarkable from saphenous vein to femoral vein. Mecobalamin 1500 μg daily was provided for 4 months, and anemia was improved as Hb 14.3g/dL, and MCV 120fL.

Keywords

Excessive alcohol consumption; Macrocytic anemia; Mean corpuscular volume (MCV); Pulse wave velocity (PWV); Vitamin B12

Introduction

For some decades, alcohol consumption has been a global problem and also a major contributor for alcohol-associated liver disease (ALD). For detecting the ALD risk, non-invasive tests (NITs) seemed to become essential tools, which offers the chance for earlier identification and also intervention to decrease the disease burden [1]. As the most widely used biomarkers for alcohol consumption, there have been several tests. They include, i) alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT) that indicate liver damage, and ii) the mean corpuscular volume (MCV), that has been a non-specific marker of alcohol misuse [2].

When a person has consumed much amount of alcohol or not, medical staffs can check the laboratory exams for quantitative assessment of alcohol use [3]. They include blood biomarkers for liver function test, such as ALT, AST, GGT, carbohydrate-deficient transferrin (CDT), mean corpuscular volume (MCV), and others. It has been crucial that MCV would be the non-specific biomarker by some factors including smoking, age, several diseases, malnutrition, liver disease, hypothyroidism, pernicious anemia, and hypothyroidism [4]. If the patient shows macrocytic anemia, detailed history-taking and thorough physical examination would be required for identifying causes. They include liver dysfunction, chronic alcoholism, dietary deficiency, malabsorptive disorders, veganism, and so on. In particular, assessing the values of vitamin B₁₂ and folate would be necessary, because folate supplementation may mask underlying vitamin B₁₂ deficiency [5,6].

Authors and collaborators have continued medical practice and research for various patients in primary care settings [7]. They include life style-related disease, atherosclerotic cardiovascular diseases (ASCVD), and psychosomatic diseases such as excessive alcohol consumption [8]. Recently, we experienced a male case with alcohol problem and macrocytic anemia. We have investigated his pathophysiology and treated him with satisfactory results. General progress and related perspectives are described in this report.

Case Presentation

History and Physicals

The patient was a 56-year-old man who visited our hospital in December 2024, complaining of fatigue and mild edema of lower extremities. His medical history included no history of surgery, no gastrointestinal diseases, and continuing usual meal habit. He did not smoke. However, he continued excessive alcohol consumption, about 1500cc of beer per day. There were no notable findings in his current condition. His stature was 162cm, 74.5kg, BMI 28.3, and waist circumference 98.5cm.

Several Examinations

A general examination was performed. No significant changes were observed in the chest X-ray and electrocardiogram. The results of the urinalysis were glucose (-), protein (+/-), occult blood (-), and general blood tests, as shown in Table 1. Among them, there were abnormal values ??for liver function tests and high values ??of uric acid. Of particular note was anemia, with Hb 8.6 g/dL and MCV 130 fL, indicating macrocytic anemia. Vitamin B₁₂ and folate concentrations were then tested. As a result, the Vitamin B₁₂ concentration was low at 137 pg/mL (180-914), the folate concentration was normal for 4.6 ng/mL (4<), and the Vitamin B₁ concentration was within the normal range at 37.0 ng/mL(21.3-81.9).

Table 1: Progress of Biochemistry data.

			2024	2025	2025
		Units	Dec	Jan	May
Liver
	AST	(U/L)	69		42
	ALT	(U/L)	28		19
	GGT	(U/L)	163		97
Renal
	UA	(mg/dL)	8.6		8.8
	BUN	(mg/dL)	-		7
	Cre	(mg/dL)	0.58		0.58
Lipids
	HDL	(mg/dL)	57		88
	LDL	(mg/dL)	31		54
	TG	(mg/dL)	159		105
Diabetes
	glucose	(mg/dL)	122		-
	HbA1c	(%)	4.8		-
CBC
	WBC	(x10*2/μL)	41		39
	RBC	(x10*4/μL)	199		378
	Hb	(g/dL)	8.6		13.9
	Ht	(%)	26.3		45.5
	MCV	(fL)	132.2		120.4
	MCH	(pg)	43.2		36.8
	MCHC	(%)	32.7		30.5
	PLT	(x10*4/μL)	25.4		14.9
	reticulo	(/1000)	-		15.7
Vitamins
	VitB12	(pg/mL)		137
	Folate	(ng/mL)		4.6
	VitB1	(ng/mL)		37.0

In January 2025, an abdominal CT scan was performed. The results showed significant fatty liver and a 10mm x 7mm renal stone in the left kidney, but no significant changes such as calcification were observed in the aorta (Figure 1). A pulse wave velocity (PWV) exam was performed. The ABI was 1.34/1.32, and the baPWV was 1413/1436 cm/sec, where both were within the normal range (Figures 2 and 3).

Figure 1: Findings of abdominal CT scan.

fatty liver in transvers aspect.
renal stone in the left kidney.
renal stone in coronal aspect.
renal stone in sagittal aspect.

Figure 2: Pulse Wave Velocity (PWV) exam ABI showed 1.34/1.32 in R/L.

Figure 3: Arteriosclerosis test by PWV baPWV showed 1413/1436 cm/sec.

Medical Problems and Progress

From mentioned above, the following medical problems were identified:

#1: Subjective symptoms are fatigue and mild leg edema,

#2: Obesity: BMI 28.3 kg/m², gradually increasing,

#3: Macrocytic anemia: Hb 8.6 g/dL, MCV 130 fL, low Vitamin B₁₂ concentration, associated with normal levels of folate and vitamin B₁.

#4: Chronic heavy alcoholism: Has continued for decades, no neuropsychiatric symptoms,

#5: Fatty liver: No sudden weight gain, gradual weight gain over decades,

#6 Hyperuricemia: UA 8.6 mg/dL, no episodes of gout attacks to date,

#7: Renal stones: No episodes of pain attacks to date, probably stones caused by uric acid.

From these data, macrocytic anemia due to vitamin B₁₂ deficiency was diagnosed, and treatment with mecobalamin 1500 μg daily as vitamin B₁₂, was started in January 2025. After 4 months, macrocytic anemia was improved as Hb 13.9 g/dL and MCV 120.4 fL. Subjective symptoms of fatigue and edema in the lower extremities were also relieved.

Just in June 2025, the right lower leg edema worsened. Previously, there were no particular findings in the same area, but this time, redness, swelling, and pain were observed. An ultrasound examination showed that there was no problem with blood flow from the right saphenous vein to the right femoral vein. Furthermore, no particular blood clots or obstruction were found, and subcutaneous swelling was observed. Consequently, the patient was diagnosed with cellulitis of the lower extremities (Figures 4). This health problem was cured with antibiotics as #8: Cellulitis.

Figure 4: Echogram in the blood stream of right lower extremities Blood flow is smooth from right saphenous vein to right femoral vein. Red & blue colors show closer & away blood streams from the probe.

Ethical Standards

This patient complied with the guideline for the Declaration in Helsinki [9]. The principle was evaluated by ethical regulation for clinical research. The guideline was from Japanese government for Ministry of Education, Culture, Sports, Science Technology and Ministry of Health, Labor and Welfare. Authors et al. set up ethical committee in the hospital, including the president, physician, head nurse, pharmacist, nutritionist, and legal professional. The staffs discussed enough for this protocol and agreed in satisfactory manner. Informed consent was obtained by the patient.

Discussion

This case had macrocytic anemia, and vitamin B₁₂ deficiency was thought to be the direct cause. The patient had no history of gastrointestinal surgery or no unbalanced diet, and had been drinking excessive alcohol for years. The medical problems in this case can be summarized as follows: #1: pretibial edema, #2: obesity, #3: macrocytic anemia, #4: chronic alcoholism, #5: fatty liver, #6 hyperuricemia, #7: renal stone, #8: cellulitis. Among these, it is thought that the fatty liver (#5) and obesity (#2) were caused by excessive alcohol drinking (#4), associated with hyperuricemia (#6) and renal stone (#7). #1 is related to a water-electrolyte imbalance, and #8 may be related to a decrease in immune function due to impaired liver function.

The main problems in this case would be alcohol consumption, elevated MCV and macrocytic anemia. Concerning these matters, various reports have been found. Alcohol may show direct hematotoxic efficacy by interfering with erythrocyte stability and cell structure [10]. The value of acetaldehyde that is a metabolite of alcohol, can bring a remarkable increase of the erythrocyte in the patient with alcohol-dependence. By alcohol misuse, the increase in MCV has been reported. Its molecular basis has not been incompletely understood. An investigation was performed for drinkers/abstainers (n=62/24) for the value of MCV [11]. Consequently, the increase in MCV was shown to be dose-dependent. Similarly, folate deficiency may be present with alcohol misuse, and then the increased value of MCV would exist [12].

The association between the genetic loci which influence MCV and related excess alcohol drinking has been unknown. A report was present from Biobank to make assessment of the relationship between them and genetic factors (n = 362 595) [13]. The method included the constructing a genetic score by SNPs of ADH1B, ADH1C and ALDH1B, and examining the assumption of acetaldehyde formation as an important determinant of MCV. As a result, increasing alcohol consumption by weekly 40g showed in a 0.30% increased value of MCV. Furthermore, MCV increased as linear mode with alcohol intake in a causal manner. Vitamin B₁₂ (cobalamin) has been a cofactor for the enzyme which transfers the carbon group from tetrahydrofolate [14]. Deficiency in either B₁₂ or folate may disrupt the division of erythrocytes to their normal size. Then, erythrocytes discontinue dividing due to deficient pyrimidines, leading to enlarged cells. From recent report, higher MCV may contribute to venous thromboembolic disease by some related mechanisms [15].

Macrocytic anemia has been a hematologic disorder with the presence of larger RBCs. About 40% of cases show anemia, and then macrocytosis often precedes anemia, it may be thought to be earlier sign of vitamin B₁₂ deficiency, and mild macrocytic anemia would be sustained for long before occurring some rapid episodes. The study was performed in a tertiary care hospital with admitted cases [16]. As a result, moderate anemia was observed in 68.5%, and severe anemia was observed in 31.5%. Among some etiologies, nutritional (22.2%), drug-induced (20.4%) and chronic alcoholism (16.7%). Mean value of Hb was 8.8 g/dL at baseline, and it elevated significantly to 10.9 g/dL after treatment for half year. Baseline MCV was 108.8, and it decreased to 97.3 for treatment. Their ratio of deficiency types showed Vit B₁₂ for 18.5%, only folate for 35.2%, and both B₁₂ and folate for 18.5%.

As recent report, the association between mean corpuscular volume (MCV) and other factors were investigated, in order to explore the macrocytosis in HFE p.C282Y (rs1800562) homozygotes [17]. The applicants were those who had p.C282Y homozygosity, and did not have special diseases such as cirrhosis, anemia, pregnancy or intaking medications influencing MCV. They received broad exams of sex, age, diabetes, alcohol consumption, serum ferritin, and swollen 2nd/3rd metacarpophalangeal (MCP) joints. As a result, participants (n=257, M/F:110/147) showed more prevalence of macrocytosis more in men with relative risk of 2.81 in men. MCV and macrocytosis were more found significantly with swollen MCP joints. Positive relationships were observed in elevated MCV and alcohol consumption.

Some limitation may be present in current report. The patient has excessive alcohol consumption, which brought macrocytic anemia and other medical and health problems. However, other possible factors are involved in the current pathophysiology, influencing to other situations. Consequently, the case will be followed up with careful attention.

In summary, 56-year-old male showed several problems of alcoholism, anemia, and other metabolic diseases. Current impressive report will become useful perspectives for clinical practice and research in the future.

Conflict of Interest: The authors declare no conflict of interest.

Funding: There was no funding received for this paper.

International Journal of Case Reports and Clinical Images